4-Methoxybenzyl alcohol → 1,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, 4-methoxyphenylmethyl ester

HRID 258147Notes

Reaction equation

HRID 258147 reaction equation
[O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:23][O:24][C:25]1[CH:30]=[CH:29]C(CO)=[CH:27][CH:26]=1>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH2:6][C:7]1[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1)=[O:4]

Participants

4

Reactant 2

HCID 77384-Methoxybenzyl alcoholHCID 867464181,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, ethyl ester

Product 1

HCID 867464221,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, 4-methoxyphenylmethyl ester

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

To a chilled (0° C.) solution of 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, ethyl ester (2.07 g) in anhydrous 4-methoxyphenylmethyl alcohol (40 ml) was added titanium (IV) ethoxide (0.54 ml) with stirring under nitrogen atmosphere. The reaction mixture was heated without reflexing for 8 hours. The 4-methoxyphenylmethyl alcohol was removed by distillation under high vacuum and the residue was dissolved in dichloromethane (200 ml). The residue was washed successively with two 100 ml portions of saturated aqueous NH4Cl solution, two 100 ml portions of saturated aqueous NaHCO3 solution and with brine, dried (Na2SO4), filtered and evaporated to yield an oil. The oil was purified by preparative HPLC (silica gel, 3% methanol in ethyl acetate as the loading solvent and eluent). A second preparative HPLC purification using 3% methanol in dichloromethane, yielded 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, 4-methoxyphenylmethyl ester (0.84 g) as an oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. customThe 4-methoxyphenylmethyl alcohol was removed by distillation under high vacuum
  3. dissolutionthe residue was dissolved in dichloromethane (200 ml)
  4. washThe residue was washed successively with two 100 ml portions of saturated aqueous NH4Cl solution, two 100 ml portions of saturated aqueous NaHCO3 solution and with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto yield an oil
  9. customThe oil was purified by preparative HPLC (silica gel, 3% methanol in ethyl acetate as the loading solvent and eluent)
  10. customA second preparative HPLC purification

Sources & evidence

ORD record
ord-6fc80945c85d4332a13a094e0e71780c
Source dataset
uspto-grants-1993_11
Patent number
US05264587

Reaction notes

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